Synaptic mechanisms and the actions of ethanol on those mechanisms were investigated in the central and peripheral nervous system using electrophysiological, optical and anatomical methods. The following synaptic pathways and their transmitters have been identified and characterized: (1) a dopaminergic pathway from substantia nigra to subthalamic nucleus; (2) a cortical-striate excitatory pathway mediated by a glutamate-like transmitter; and (3) muscarinic cholinergic inhibitory and excitatory pathways in sympathetic ganglia. Pharmacologic analysis with muscarinic antagonists suggests that the muscarinic inhibitory response involves a different muscarinic receptor subtype than the muscarinic excitatory response. Voltage-clamp analysis of the excitatory muscarinic postsynaptic action revealed two voltage-dependent conductance changes - a decreased outward potassium current at membrane potentials positive to -50mV and an increased inward current, probably carried by sodium ions, at membrane potentials negative to -70mV. Ethanol, 50-200mM, increased spontaneous transmitter release and decreased evoked transmitter release. Theophylline, 5mM, induced a periodic intracellular release of calcium ions. This intracellular release of calcium was facilitated by ethanol, 50-200mM. Electron microscopic observations suggest that the calcium is released from subsurface cisternae. An ethanol-induced intracellular release of calcium ions in nerve terminals may explain the effects of ethanol on synaptic transmission. The significance of the project lies in the fact that characterization of synaptic mechanisms and the actions of ethanol on those mechanisms holds the promise of increasing our understanding of the cellular basis of ethanol's actions in the nervous system.